TAB2 Scaffolds TAK1 and NLK in Repressing Canonical Wnt Signaling
Open accessAbstract
The TAK1-NLK cascade is a mitogen-activated protein kinase-related pathway that plays an inhibitory role in canonical Wnt/beta-catenin signaling through regulating the LEF1/TCF family transcriptional factors. TAB2 (TAK1-binding protein 2) is a putative TAK1 interacting protein that is involved in the regulation of TAK1. Here, we found that TAB2 could directly interact with NLK and function as a scaffold protein to facilitate the interaction between TAK1 and NLK. Knocking down TAB2 using small interfering RNA abolished the interaction of TAK1 with NLK in mammalian cells. The intermediate region (residues 292-417) of TAB2 was mapped for its binding to NLK. TAB2-DeltaM, a TAB2 mutant lacking this region, showed a lower affinity for NLK and became defective in its scaffolding function. In addition, TAB2, but not TAB2-DeltaM, mediated TAK1-dependent activation of NLK and LEF1 polyubiquitylation, resulting in the inhibition of canonical Wnt signaling. Moreover, Wnt3a stimulation led to an increase in the interaction of TAB2 with NLK and the formation of a TAK1.TAB2.NLK complex, suggesting that this TAK1-TAB2-NLK pathway may constitute a negative feedback mechanism for canonical Wnt signaling.
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Another mechanism of antagonising Wnt/β-catenin signalling by NLK is through activation of the TAK1-mediated non-canonical Wnt pathway and TAB2.
“Another mechanism of antagonising the Wnt/β-catenin signalling pathway by NLK is through activation of the transforming growth factor beta-activated kinase 1 (TAK1)-mediated non-canonical Wnt pathway and TAK1-binding protein 2 (TAB2).”
From Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies (2020) · cites this paper as [18]
The paper reports that TAB2 scaffolds TAK1 and NLK, enabling NLK activation and inhibition of canonical Wnt signaling (opening summary; Results and Discussion). It does not establish this as activation of a specifically non-canonical Wnt pathway: its experiments use Wnt3a stimulation, and it describes the resulting cascade as possible negative feedback on canonical signaling. (LLM, conf=0.86)
Experimental — accuracy not yet measuredTAB2 can directly interact with NLK as a scaffold protein, thereby enabling the interaction between NLK and TAK1.
“It was shown that TAB2 can directly interact with NLK as a scaffold protein, thereby enabling the interaction between NLK and TAK1 [18].”
From Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies (2020) · cites this paper as [18]
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Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies
Daams, R., & Massoumi, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239203 · Cited by 21 · see citing works
“Another mechanism of antagonising the Wnt/β-catenin signalling pathway by NLK is through activation of the transforming growth factor beta-activated kinase 1 (TAK1)-mediated non-canonical Wnt pathway and TAK1-binding protein 2 (TAB2).”
BackgroundInfluential
- Authors
- Li, M., Wang, H., Huang, T., Wang, J., Ding, Y., Li, Z., Zhang, J., & Li, L.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Li, Lin
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 285
- Issue
- 18
- Pages
- 13397-13404
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2859499
- OpenAlex
- W1997989974
- Cited by
- 32
- References
- 5
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2021: 4 · 2020: 4 · 2019: 1 · 2017: 3 · 2016: 2 · 2014: 3 · 2013: 2 · 2012: 4
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- TAB2, TAK1, Nemo-like kinase, canonical Wnt/β-catenin pathway, scaffold proteins, protein-protein interaction, negative feedback regulation, Wnt3a
- MeSH terms
- MAP Kinase Kinase Kinase 7, Animals, Cell Line, Humans, Mutation, Signal Transduction, Protein Serine-Threonine Kinases, Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinases, Multiprotein Complexes, Adaptor Proteins, Signal Transducing, Wnt Proteins, beta Catenin, Mice, Gene Knockdown Techniques, Wnt3 Protein, Wnt3A Protein
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